PMID- 32493428
OWN - NLM
STAT- MEDLINE
DCOM- 20210618
LR  - 20220531
IS  - 1757-6512 (Electronic)
IS  - 1757-6512 (Linking)
VI  - 11
IP  - 1
DP  - 2020 Jun 3
TI  - SHP2 mutations induce precocious gliogenesis of Noonan syndrome-derived iPSCs 
      during neural development in vitro.
PG  - 209
LID - 10.1186/s13287-020-01709-4 [doi]
LID - 209
AB  - BACKGROUND: Noonan syndrome (NS) is a developmental disorder caused by mutations 
      of Src homology 2 domain-containing protein tyrosine phosphatase 2 (SHP2). 
      Although NS patients have diverse neurological manifestations, the mechanisms 
      underlying the involvement of SHP2 mutations in neurological dysfunction remain 
      elusive. METHODS: Induced pluripotent stem cells generated from dermal 
      fibroblasts of three NS-patients (NS-iPSCs) differentiated to the neural cells by 
      using two different culture systems, 2D- and 3D-cultured systems in vitro. 
      RESULTS: Here we represent that SHP2 mutations cause aberrant neural development. 
      The NS-iPSCs exhibited impaired development of EBs in which BMP and TGF-beta 
      signalings were activated. Defective early neuroectodermal development of 
      NS-iPSCs recovered by inhibition of both signalings and further differentiated 
      into NPCs. Intriguingly, neural cells developed from NS-NPCs exhibited abundancy 
      of the glial cells, neurites of neuronal cells, and low electrophysiological 
      property. Those aberrant phenotypes were also detected in NS-cerebral organoids. 
      SHP2 inhibition in the NS-NPCs and NS-cerebral organoids ameliorated those 
      anomalies such as biased glial differentiation and low neural activity. 
      CONCLUSION: Our findings demonstrate that SHP2 mutations contribute to precocious 
      gliogenesis in NS-iPSCs during neural development in vitro.
FAU - Ju, Younghee
AU  - Ju Y
AD  - Department of Biological Sciences, KAIST, Daejeon, 34141, Republic of Korea.
FAU - Park, Jun Sung
AU  - Park JS
AD  - Graduate School of Medical Science and Engineering, KAIST, Daejeon, 34141, 
      Republic of Korea.
FAU - Kim, Daejeong
AU  - Kim D
AD  - Department of Bio and Brain Engineering, KAIST, Daejeon, 34141, Republic of 
      Korea.
FAU - Kim, Bumsoo
AU  - Kim B
AD  - Department of Biological Sciences, KAIST, Daejeon, 34141, Republic of Korea.
FAU - Lee, Jeong Ho
AU  - Lee JH
AD  - Graduate School of Medical Science and Engineering, KAIST, Daejeon, 34141, 
      Republic of Korea.
FAU - Nam, Yoonkey
AU  - Nam Y
AD  - Department of Bio and Brain Engineering, KAIST, Daejeon, 34141, Republic of 
      Korea.
FAU - Yoo, Han-Wook
AU  - Yoo HW
AD  - Department of Pediatrics, Asan Medical Center Children's Hospital, University of 
      Ulsan College of Medicine, Seoul, 05505, Republic of Korea.
FAU - Lee, Beom Hee
AU  - Lee BH
AD  - Department of Pediatrics, Asan Medical Center Children's Hospital, University of 
      Ulsan College of Medicine, Seoul, 05505, Republic of Korea.
FAU - Han, Yong-Mahn
AU  - Han YM
AUID- ORCID: 0000-0002-1270-0413
AD  - Department of Biological Sciences, KAIST, Daejeon, 34141, Republic of Korea. 
      ymhan@kaist.ac.kr.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20200603
PL  - England
TA  - Stem Cell Res Ther
JT  - Stem cell research & therapy
JID - 101527581
RN  - EC 3.1.3.48 (PTPN11 protein, human)
RN  - EC 3.1.3.48 (Protein Tyrosine Phosphatase, Non-Receptor Type 11)
SB  - IM
EIN - Stem Cell Res Ther. 2020 Jul 16;11(1):282. PMID: 32669122
MH  - Humans
MH  - *Induced Pluripotent Stem Cells/metabolism
MH  - Mutation
MH  - *Noonan Syndrome/genetics
MH  - Protein Tyrosine Phosphatase, Non-Receptor Type 11/genetics/metabolism
MH  - Signal Transduction
PMC - PMC7268229
OTO - NOTNLM
OT  - Cerebral organoids
OT  - Gliogenesis
OT  - Induced pluripotent stem cells
OT  - Neural development
OT  - Noonan syndrome
OT  - SHP2 mutations
COIS- The authors indicate no potential conflicts of interest.
EDAT- 2020/06/05 06:00
MHDA- 2021/06/22 06:00
PMCR- 2020/06/03
CRDT- 2020/06/05 06:00
PHST- 2019/12/18 00:00 [received]
PHST- 2020/05/06 00:00 [accepted]
PHST- 2020/03/20 00:00 [revised]
PHST- 2020/06/05 06:00 [entrez]
PHST- 2020/06/05 06:00 [pubmed]
PHST- 2021/06/22 06:00 [medline]
PHST- 2020/06/03 00:00 [pmc-release]
AID - 10.1186/s13287-020-01709-4 [pii]
AID - 1709 [pii]
AID - 10.1186/s13287-020-01709-4 [doi]
PST - epublish
SO  - Stem Cell Res Ther. 2020 Jun 3;11(1):209. doi: 10.1186/s13287-020-01709-4.